Immunosignatures can predict vaccine efficacy paper 02-28-2014d1558

2015-01-13

-http://www.pnas.org/content/110/46/18614.short
-"C:\Users\kurtw_000\Box Sync\DocDR\2013\12-11-2013d0915\Immunosignatures can predict vaccine efficacy.pdf"
-paper by Bart

-By using
a mouse in?uenza infection, we show that the immunosignaturing
of a natural infection can be used to discriminate a protective from
nonprotective vaccine.
- Further, we demonstrate that an immuno-
signature can determine which mice receiving the same vaccine
will survive.
-Finally, we show that the peptides comprising the
correlate signatures of protection can be used to identify possible
epitopes in the in?uenza virus proteome that are correlates
of protection.
-data reported in this paper have been de-
posited in the Gene Expression Omnibus (GEO) database,
-Correlates of protection are immune responses that are speci ? c
products of the vaccine and statistically associated with pro-
tection
-Here we eval-
uate whether immunosignatures can characterize and stratify
vaccines into those that are ef ? cacious and those that are not.
-On a ? ner scale, individual
monoclonal antibodies bind to a surprisingly large number of random-sequence peptides and are detectable within a complex
mixture of competing antibodies (7, 12)
-in?uenza model, A/PR/
8/34
-study plan: 5 groups of 10 female BALB/c mice were immunized.  Challenged with H1N1 A/PR/8/34 (PR8 virus).  3 groups vaccinated with inactivated viruses: killed PR8 and the two seasonal vaccines:  A/Wisconsin/67/2005 (H3N2) and B/
Malaysia/2506/2004.  Mock vaccination group. 5th group vaccinated a single time with a sublethal dose of live PR8 virus
-The two seasonal vaccines were partially protective, re-
sulting in 60% and 80% survival.
-Live and Inactive In?uenza Immunizations Produce Different Immu-
nosignatures
-The Immunosignature Can Distinguish Closely Related Vaccines
-The Immunosignature of a Known Protective Response Can Predict
Outcome Following Challenge
--SAM algorithm uses a permuted t-test
-Seasonal Vaccine Recipients Have Distinct Immunosignatures, Which
Correlate with Outcome Following PR8 Challenge
--Hamming distance
-The Immunosignature Can Be Bioinformatically Tracked Back to the
Epitopes on the A/PR/8/34 Proteins.
-To extend the analysis of potential correlates of protection, an
informatics analysis of the 94 peptides distinguishing the sur-
viving and nonsurviving mice from each other was conducted.
Thirty-eight of these peptides that were increasingly recognized
in the survivors vs. those that died.
- Systems vaccinology
-Apart from vaccine development, the ability to predict whether
an individual would survive a lethal infection may have appli-
cation in the public health response to pandemic disease

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